Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deep vein thrombosis in man presents a considerable clinical challenge. Despite the availability of prophylactic measures, therapeutic thrombolysis is often necessary, but is difficult and hazardous. Treatments have included the administration of plasmin, other less specific proteolytic enzymes, the indirect plasminogen activator, streptokinase, and the direct activators, urokinase and streptokinase-human plasmin complex. All these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application. The enzyme components of the coagulation and fibrinolytic pathways can, in general, be classed as serine proteases, with a catalytic mechanism which operates via acyl-enzyme intermediates. Chase and Shaw showed that p-nitrophenyl-p'-guanidinobenzoate could specifically acylate the active centre of trypsin-like enzymes, giving rise to a stable p-guanidinobenzoyl enzyme and other stable acyl-enzymes have since been described. We report here the fibrinolytic use of acylated derivatives of plasmin (E.C.3.4.21.7) and streptokinase-plasmin(ogen) complexes.
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PMID:Fibrinolysis with acyl-enzymes: a new approach to thrombolytic therapy. 721 37

Thrombolytic therapy mimics and enhances physiological fibrinolysis. The following substances are presently available for clinical use: the nonphysiological thrombolytics streptokinase, the APSAC (acylated plasminogen-streptokinase activator complex), the physiological plasminogen activators urokinase and tissue plasminogen activator (t-PA). Whereas the first three systematically activate the fibrinolytic system, t-PA possesses relative fibrin selectivity. The fibrin-selective active pro-urokinase has not yet been officially approved for the treatment of thromboembolic diseases, but it is being clinically tested. Fibrinolytic therapy has an established place in the management of acute myocardial infarction and of massive pulmonary embolism. When an acute deep venous thrombosis is diagnosed with a proximal extension into the popliteal vein, thrombolytic therapy is clearly superior to heparin. The lysis has proven to be an effective form of treatment of peripheral occlusive arterial disease. Local thrombolytic therapy is an option for acute and chronic femoro-popliteal occlusions involving the trifurcation into the calf arteries and for embolic occlusions of the same segment in patients with contraindications to surgical therapy. First study results of thrombolytic therapy of stroke are promising.
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PMID:[Fibrinolytic agents--who benefits when?]. 748 76

Safety and efficacy of the thrombolytic agent pro-urokinase (pro-UK) in the treatment of deep vein thrombosis of the lower limbs (DVT) have been investigated in an open, uncontrolled, pilot study. Fifteen patients were infused with 800.000 IU (5 mg)/h of pro-UK over 24 h (120 mg), together with unfractionated heparin adjusted to maintain the activated partial thromboplastin time between 1.5 and 2.5 times the basal value. Efficacy was assessed comparing venographic changes in the 11 evaluable limbs before and after pro-UK infusion. The Marder score decreased from a median pre-thrombolysis value of 28 (range 4-40) to 16 (3-38) (p < 0.05). One major hemorrhagic event (retroperitoneal bleeding 4 days after the end of the pro-UK infusion) occurred. Fibrinogen, alpha 2-antiplasmin and plasminogen significantly decreased from baseline values after 12 and 24 h, fibrin(ogen) degradation products significantly increased. Changes in hemostasis parameters were unrelated to thrombolytic efficacy. The results of this pilot study indicate that pro-UK is thrombolytic in DVT and that it can be administered simultaneously with conventional heparin treatment.
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PMID:A pilot study of pro-urokinase in the treatment of deep vein thrombosis. 753 76

We introduce a new fibrin plate assay performed in microtiter plates. By means of spectroscopic studies we optimized the structure of the fibrin gel and then used the optimized fibrin gel to determine plasminogen activator activity. Plasminogen activator solutions were applied on top of the fibrin gel, and the absorbance of the gel was recorded at 405 nm. After incubation for 17 h at 25 degrees C, the absorbance was measured again. The difference in absorbance was proportional to the concentration of plasminogen activator, such that the dose-response curves were linear when the difference in absorbance was plotted as a function of the logarithmic concentration of plasminogen activator. We assayed both tissue-type and urokinase-type plasminogen activator activity. The intraassay CV was < 4.7% (n = 20); the interassay CV was < 3.1% (n = 15). Using the optimized procedure, we modified the assay for determination of plasma-coagulum lysis time in human plasma. We established a reference interval for lysis time in apparently healthy subjects of 75 to 201 ks. Patients with deep vein thrombosis showed significantly (P = 0.013) higher values.
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PMID:Plasminogen activator activity and plasma-coagulum lysis measured by use of optimized fibrin gel structure preformed in microtiter plates. 754 22

Patients with a recent (less than 10 days) proximal deep vein thrombosis of the leg or pelvis are candidates for thrombolysis as the major benefit over heparin seems to be the prevention of the postphlebitic limb, an aim which is still not proven in a satisfactory manner. Nonocclusive thrombi appear to lyse more readily than occlusive thrombi. For this indication the optimal dose regimens for the three thrombolytic drugs (streptokinase, urokinase, alteplase) are not established. Acute massive pulmonary embolism with hypotension or shock should be treated with thrombolytic drugs and, pending the outcome in the first hour, be considered for pulmonary embolectomy. Major acute pulmonary embolism with haemodynamic instability responds well to thrombolysis. Whether thrombolysis is superior to heparin in subacute intermediate pulmonary embolism has not been proven unequivocally in terms of mortality or clinically important endpoints. Systemic administration of thrombolytic drugs for peripheral arterial occlusion has been abandoned for catheter-directed and intraoperative intra-arterial repeated bolus or short-term infusions. The efficacy and safety of intravenous thrombolytic treatment following a major ischaemic stroke is presently being tested in large scale trials; its use must be restricted to experimental protocols.
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PMID:Thrombolytic therapy of non-cardiac disorders. 754 71

The incidence of deep venous thrombosis or pulmonary embolism after lung or heart-lung transplantation has not been well defined. Pulmonary embolism may be of particular concern in the postoperative period owing to an inadequately developed or absent collateral bronchial circulation and potential risk of pulmonary infarction. Fourteen (12.1%) of 116 patients undergoing either lung (n = 87) or heart-lung (n = 29) transplantation developed thromboembolic complications 10 days to 36 months after operation. Deep vein thrombosis developed in nine patients, including three with upper body thrombosis related to indwelling central venous catheters. Seven patients (6%) had pulmonary embolism, and three of them died. Resolution of pulmonary embolism was successfully accomplished by selective pulmonary artery infusion of urokinase in three patients without complications. Our experience indicates that deep vein thrombosis and pulmonary embolism are significant problems after lung transplantation. Mortality is high in those patients in whom pulmonary embolism develops. Therefore, a comprehensive prevention protocol is warranted.
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PMID:Deep venous thrombosis and pulmonary embolism after lung transplantation. 763 73

Five months after a cadaveric renal transplants a 69-year-old man was admitted with caval, iliac, and renal allograft vein thrombosis that occurred in the setting of a previously placed caval filter. The patient's urine output and renal function deteriorated rapidly. Thrombolytic therapy with urokinase was begun, and lysis of the thrombus occurred in 72 hours. The patient's renal function returned to baseline, and the transplant was salvaged. Moreover lower extremity venous patency and valvular function were maintained. We report the case and review the literature on thrombolytic therapy for renal allograft vein and lower extremity deep venous thrombosis.
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PMID:Salvage of renal allograft function and lower extremity venous patency with thrombolytic therapy: case report and review of the literature. 757 80

A 52-year-old man had recurrent pulmonary thrombo embolism following fracture in tibia and subsequent deep vein thrombosis. One episode of massive pulmonary embolism with haemodynamic compromise was managed successfully by balloon compression of the thrombus and thrombolysis with urokinase. Patient was rehabilitated in his previous profession.
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PMID:Intra pulmonary thrombolytic therapy with balloon dilatation in recurrent acute pulmonary embolism. 773 2

During the last 10 years anticoagulant (AC) therapy and thrombolytic treatment of venous thromboembolism (VT) have been evaluated in randomized studies. Adjusted subcutaneous (s.c.) heparin and low molecular weight heparin (LMWH) are found at least as effective as intravenous (i.v.) infusion of heparin in deep venous thrombosis (DVT) without an increased bleeding risk. In pulmonary embolism (PE) randomized trials assessing the efficacy of s.c. heparin and LMWH are missing. Oral AC-treatment can be initiated from the first or second day in VT. The recommended duration is three months for medical patients, and 4 weeks seem appropriate for surgical patients that are completely mobilized and without persisting predisposing factors. Long-term efficacy of thrombolytic treatment of DVT has only been assessed in small trials showing a trend towards reduced risk of developing chronic venous insufficiency. Short-term thrombolytic treatment of DVT is evaluated in ongoing trials. In the treatment of PE short-term thrombolysis with either t-PA or urokinase is found to be as effective as long-term thrombolytic treatment with a reduced bleeding risk. Thrombolytic therapy rapidly reduces embolic mass and stabilizes haemodynamics, but mortality and long-term efficacy of thrombolysis and AC-treatment versus AC-treatment alone in PE are being assessed in ongoing studies.
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PMID:[Anticoagulant and thrombolytic therapy in deep venous thrombosis and pulmonary embolism]. 778 97

Massive deep venous thrombosis with marked venous outflow obstruction can result in limb loss or end-organ injury. Systemically administered drugs may not reach thrombi in therapeutic concentrations and surgical and thrombolytic strategies carry a small but real risk of pulmonary embolus--similar to the risks with anticoagulation alone. We therefore developed a strategy in which catheter-directed thrombolysis was used to deliver high concentrations of a plasminogen activator directly to the thrombus combined with placement of a downstream Greenfield filter to protect patients from pulmonary embolus. From 1984 to 1993 six patients were treated with this regimen. All had severe symptoms of less than 4 days' duration. On radiologic evaluation four patients had large iliofemoral and/or inferior vena cava thrombosis, one had subclavian/innominate vein thrombosis, and one had transplant renal vein/iliofemoral/inferior vena cava thrombosis. A Greenfield filter was first placed downstream prior to imbedding an infusion catheter in the greatest mass of thrombus for subsequent infusion of urokinase (n = 4) or streptokinase (n = 2). In four patients the catheter traversed the Greenfield filter. All patients were given bolus lytic therapy followed by maintenance infusions ranging in duration from 24 hours to 12 days. Five patients remained on heparin simultaneously. Clot lysis was achieved in all patients with hemodynamic, symptomatic, and arteriographic improvement. There were no deaths, pulmonary emboli, or complications of filter placement. One patient had minor bleeding at the puncture site and another had catheter-related infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Catheter-directed thrombolysis following vena cava filtration for severe deep venous thrombosis. 786 98


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